Colorectal cancer (CRC) is a preventable disease, but still claims many lives because we have yet to optimally implement preventive therapies. One of the biggest challenges is the fact that CRC is not a single uniform disease, but rather a complex multifactoral process with variable expression in susceptible individuals. Developing safe and effective chemoprevention for CRC requires understanding the nature of early colorectal tumorigenesis in actual patients at risk for this disease and following through to test new mechanistically valid chemopreventive agents in human clinical trials. Few research centers have the experienced investigators, resources, and supportive infrastructure required for successful completion of cancer chemoprevention trials. As a result, there is a great need to train new investigators to conduct this important research. Dr. Monica Bertagnolli is an experienced translational researcher in colorectal cancer (CRC) prevention. She is the Lead Principal Investigator of the recently completed Adenoma Prevention with Celecoxib (APC) Trial, a randomized placebo-controlled study of more than 2000 patients at high risk for CRC. She also directs a laboratory studying the biology of pre-malignant adenomas and the tissue-specific effects of chemopreventive compounds. This proposal for an established investigator career development award outlines a plan for Dr. Bertagnolli to spend a significant amount of time over the next 5 years mentoring junior faculty members in cancer prevention research. She will use the considerable clinical data and tissue resources of the APC Trial to provide advisees with the raw materials necessary to conduct studies of modifiable factors in CRC development and chemopreventive drug response. She also establish a multidisciplinary forum for presentation, discussion, and critique of ongoing work in Gl cancer prevention, aided by senior Dana Farber-Harvard Cancer Center investigators and outside consultants. Conducting high quality translational research in a manner that optimizes educational potential is extremely time consuming, and Dr. Bertagnolli is one of the few individuals who can succeed in this task. The support provided by this award will allow Dr. Bertagnolli to complete key research projects using APC Trial resources in a manner that facilitates maturation of junior faculty into independent researchers in cancer prevention.